Cargando…

Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status

KEY POINTS: Few reports have explored the possibility of involvement of non‐inflammatory factors in lacrimal hyposecretion in Sjögren's syndrome (SS). RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated in the lacrimal gland of SS model male mice (NOD...

Descripción completa

Detalles Bibliográficos
Autores principales: Ohno, Yuta, Satoh, Keitaro, Shitara, Akiko, Into, Takeshi, Kashimata, Masanori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693353/
https://www.ncbi.nlm.nih.gov/pubmed/32780506
http://dx.doi.org/10.1113/JP280090
_version_ 1783614724486725632
author Ohno, Yuta
Satoh, Keitaro
Shitara, Akiko
Into, Takeshi
Kashimata, Masanori
author_facet Ohno, Yuta
Satoh, Keitaro
Shitara, Akiko
Into, Takeshi
Kashimata, Masanori
author_sort Ohno, Yuta
collection PubMed
description KEY POINTS: Few reports have explored the possibility of involvement of non‐inflammatory factors in lacrimal hyposecretion in Sjögren's syndrome (SS). RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated in the lacrimal gland of SS model male mice (NOD mice) after onset of lacrimal hyposecretion and dacryoadenitis. Even in non‐dacryoadenitis‐type NOD mice, tear secretion and arginase 1 expression remained low. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. The results indicate that a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. ABSTRACT: Lacrimal fluid (tears) is important for preservation of the ocular surface, and thus lacrimal hyposecretion in Sjögren's syndrome (SS) leads to reduced quality of life. However, the cause(s) of lacrimal hyposecretion remains unknown, even though many studies have been conducted from the perspective of inflammation. Here, we hypothesized that a non‐inflammatory factor induces lacrimal hyposecretion in SS pathology, and to elucidate such a factor, we conducted transcriptome analysis of the lacrimal glands in male non‐obese diabetic (NOD) mice as an SS model. The NOD mice showed inflammatory cell infiltration and decreased pilocarpine‐induced tear secretion at and after 6 weeks of age compared to age‐matched BALB/c mice. RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated, whereas many genes relating to inflammation were upregulated, in the lacrimal glands of male NOD mice after onset of lacrimal hyposecretion and dacryoadenitis (lacrimal gland inflammation). Changes in the level of arginase 1 expression were confirmed by real‐time RT‐PCR and western blot analysis. Furthermore, non‐dacryoadenitis‐type NOD mice were used to investigate the relationships among arginase 1 expression, lacrimal hyposecretion and dacryoadenitis. Interestingly, these NOD mice retained the phenotype of dacryoadenitis with regard to tear secretion and arginase 1 expression level. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. In conclusion, a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. These results shed light on the pathophysiological role of arginase 1 in SS (dry eye).
format Online
Article
Text
id pubmed-7693353
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-76933532020-12-11 Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status Ohno, Yuta Satoh, Keitaro Shitara, Akiko Into, Takeshi Kashimata, Masanori J Physiol Molecular and Cellular KEY POINTS: Few reports have explored the possibility of involvement of non‐inflammatory factors in lacrimal hyposecretion in Sjögren's syndrome (SS). RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated in the lacrimal gland of SS model male mice (NOD mice) after onset of lacrimal hyposecretion and dacryoadenitis. Even in non‐dacryoadenitis‐type NOD mice, tear secretion and arginase 1 expression remained low. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. The results indicate that a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. ABSTRACT: Lacrimal fluid (tears) is important for preservation of the ocular surface, and thus lacrimal hyposecretion in Sjögren's syndrome (SS) leads to reduced quality of life. However, the cause(s) of lacrimal hyposecretion remains unknown, even though many studies have been conducted from the perspective of inflammation. Here, we hypothesized that a non‐inflammatory factor induces lacrimal hyposecretion in SS pathology, and to elucidate such a factor, we conducted transcriptome analysis of the lacrimal glands in male non‐obese diabetic (NOD) mice as an SS model. The NOD mice showed inflammatory cell infiltration and decreased pilocarpine‐induced tear secretion at and after 6 weeks of age compared to age‐matched BALB/c mice. RNA‐sequencing analysis revealed that only four genes, including arginase 1, were downregulated, whereas many genes relating to inflammation were upregulated, in the lacrimal glands of male NOD mice after onset of lacrimal hyposecretion and dacryoadenitis (lacrimal gland inflammation). Changes in the level of arginase 1 expression were confirmed by real‐time RT‐PCR and western blot analysis. Furthermore, non‐dacryoadenitis‐type NOD mice were used to investigate the relationships among arginase 1 expression, lacrimal hyposecretion and dacryoadenitis. Interestingly, these NOD mice retained the phenotype of dacryoadenitis with regard to tear secretion and arginase 1 expression level. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. In conclusion, a non‐inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. These results shed light on the pathophysiological role of arginase 1 in SS (dry eye). John Wiley and Sons Inc. 2020-08-29 2020-11-01 /pmc/articles/PMC7693353/ /pubmed/32780506 http://dx.doi.org/10.1113/JP280090 Text en © 2020 The Authors. The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Molecular and Cellular
Ohno, Yuta
Satoh, Keitaro
Shitara, Akiko
Into, Takeshi
Kashimata, Masanori
Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title_full Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title_fullStr Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title_full_unstemmed Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title_short Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's syndrome, regardless of dacryoadenitis status
title_sort arginase 1 is involved in lacrimal hyposecretion in male nod mice, a model of sjögren's syndrome, regardless of dacryoadenitis status
topic Molecular and Cellular
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693353/
https://www.ncbi.nlm.nih.gov/pubmed/32780506
http://dx.doi.org/10.1113/JP280090
work_keys_str_mv AT ohnoyuta arginase1isinvolvedinlacrimalhyposecretioninmalenodmiceamodelofsjogrenssyndromeregardlessofdacryoadenitisstatus
AT satohkeitaro arginase1isinvolvedinlacrimalhyposecretioninmalenodmiceamodelofsjogrenssyndromeregardlessofdacryoadenitisstatus
AT shitaraakiko arginase1isinvolvedinlacrimalhyposecretioninmalenodmiceamodelofsjogrenssyndromeregardlessofdacryoadenitisstatus
AT intotakeshi arginase1isinvolvedinlacrimalhyposecretioninmalenodmiceamodelofsjogrenssyndromeregardlessofdacryoadenitisstatus
AT kashimatamasanori arginase1isinvolvedinlacrimalhyposecretioninmalenodmiceamodelofsjogrenssyndromeregardlessofdacryoadenitisstatus